On 2020-09-01 19:02:36, user Giovanni Lentini wrote:
I'd like to congratulate the Authors who demonstrated that our hypotheses were sound (cfr. Lentini et al. COVID-19, Chloroquine Repurposing, and Cardiac Safety Concern: Chirality Might Help. Molecules 2020, 25 (8). https://doi.org/10.3390/mol...
On 2020-09-01 17:37:34, user Marcos Fernando Basso wrote:
Dear authors,
Please, let me know how I can access the genome database of the brachiaria.<br /> Thank you so much.
On 2020-09-01 17:01:16, user Diana Duarte wrote:
Thanks for the interest in this research. After some work, a published version will come soon! I will keep you updated.
On 2020-08-27 15:27:22, user Diana Duarte wrote:
Thanks for the interest in this research. After some work, a published version will come soon! I will keep you updated.
On 2020-09-01 16:18:19, user Ed Hollox wrote:
Nice work. Good to confirm what we found in figures S6 and S7 - using a very similar approach - concerning the dispersed CNV at 8p23.1 either end of the inversion. See https://www.pnas.org/conten...
On 2020-09-01 16:08:29, user carlos wrote:
Figures are rendered in very bad quality. It is not possible to read the text within.<br /> Can you please reupload figures?
On 2020-09-01 15:58:18, user Mariano Avino wrote:
We were not able to reproduce the experimental data of this work, so we have decided to conduct other experimental tests. This is the reason for delaying the publication of this paper. Mariano Avino
On 2020-09-01 15:05:58, user Ben Sprung wrote:
SI is currently available at https://www.dropbox.com/s/e...
On 2020-09-01 13:37:11, user Solveig Jore wrote:
Is it possible to get a better and more detailed description of Materials & Methods. We are not able to understand it the way it is described here.
On 2020-08-24 03:57:25, user Brett Edgerton wrote:
Very nice piece of research. It confirms the potential that I have been discussing for the past several months since it became clear that meat processing facilities are the sites of significant clusters globally. My congratulations and appreciation to the authors for conducting these vital studies.
On 2020-08-21 20:13:28, user Andrew wrote:
if cells that produce antibodies are multiplied, then there will be a vaccine against covid-19
On 2020-09-01 10:02:59, user Silvia Preziuso wrote:
If you like, please read my recent paper "Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Exhibits High Predicted Binding Affinity to ACE2 from Lagomorphs (Rabbits and Pikas)" at https://doi.org/10.3390/ani...
On 2020-09-01 09:25:13, user Sean Munro wrote:
I not think that this paper reports an "interactome" - it reports a "proximityome". BioID will label many proteins that simpy happen to be in the same compartment as the protein tagged with the biotin ligase without neccessarily interacting with them. Thus a BioID version of a SARS-CoV-2 protein that is in the Golgi will biotinylate many Golgi residents even if it only interacts with a subset of with them.
On 2020-08-31 22:21:33, user Rubayetul Alam wrote:
Could you please tell here that from where the accession no was derived?<br /> Thanks
On 2020-08-14 12:38:44, user qx jiang wrote:
The structures are pretty good and record-making. <br /> The channel behavior, ion selectivity sequence, and electrical recordings, esp. S2 appear strange without matching regular opening/closing events.
On 2020-08-31 18:28:54, user Alyssa Long wrote:
This is a very interesting and exciting technology/assay.<br /> The Caspary and Kahn labs at Emory covered this preprint in a recent virtual<br /> journal club. During the discussion, we had a couple questions and comments we<br /> wanted to share.
-When talking about grouping proteins into tiers, it was unclear what was meant by a “dataset”. As a group, we concluded that the three replicates/sets of cilia-APEX2 (left column in Fig 2A) were each considered a dataset – so if a protein was identified in only two of the three replicates, it would be put into tier 2, while a protein in all three<br /> replicates would be classified as tier 1. Is this interpretation correct?<br /> Perhaps the tier classifications and/or the data collection could be elaborated<br /> upon (maybe in the Methods section).
-Why were no axonemal components identified with this technique? Presumably this is because your APEX2 fusion protein is on the ciliary membrane and the distance to the axoneme exceeds the sphere of reactive oxygen species generated. It might be worth a brief comment or perhaps even speculate in the Discussion as to the outcome of an axonemal probe?
-Figure 4C shows time after Shh addition in hours – but this should be minutes.
-In Fig 5 (PKA-Rialpha, GPR161, and cAMP) – the model proposes an association of subunits and formation of a holoenzyme, but there’s no experimental evidence to support this.
-Regarding the interpretation of data presented in Fig 6, you say activation of SSTR3 is sufficient to recruit PALD1 to cilia and suggest that both PALD1 entry into and GPR161 exit from cilia are in response to “drops in ciliary cAMP levels”. This comparison is confusing as GPR161 is G alpha s whereas SSTR3 is G alpha i. The model only seems to make sense if you lose GPR161-Gas from cilia, or if you activate Smo-Gai, but not if<br /> you lose SSTR3-Gai in cilia.
-Figure 7F: the legend says the primary cilia are represented in blue; I see two green cilia icons and assumed the ones in the left column with the center dots are motile cilia.
-In Fig 8B, Paladin appears to run at about 100kD by western blot; this contrasts with the blot shown in Fig 7A, where it looks just a little bigger than 80kD. Maybe this is due to use of a different protein ladder or a labelling error? Could you also indicate which of the lower bands is the specific Gli3R band (or which is nonspecific) that was quantitated?
-For Fig 8, it would be nice to see the downstream effects of Paladin deletion (Q-RTPCR of Shh targets like Gli1 or Ptch1) in addition to the changes in Gli3 processing and ciliary protein localization. This would add weight to the statement that “PALD1-deficient IMCD3 cells spontaneously activate the Hh pathway” and the conclusion that PALD1 is an attenuator of the pathway.
-Throughout the manuscript, “Shh conditioned medium” or “Shh” should be adjusted to “Shh-N conditioned medium” or “Shh-N”(as specified in the Methods) for explicit clarity – the Shh-N variant does not have the cholesterol modification found on the endogenous ligand. Perhaps specifying which lipid modifications do/don’t occur, or how this differs from endogenous ligand or SAG stimulation, would be useful.
We look forward to additional applications of this technology as well as the construction of “specialized” APEX2 variants (such as CiliaTip-APEX).
--Alyssa Long, PhD (Caspary Lab)
On 2020-08-31 18:13:58, user Adrian Roitberg wrote:
This paper belongs to the category of ‘impossible to reproduce’. The ligands the author ends up measuring are identified only by their chemical formula, which is the same as identifying them as magical creatures.
On 2020-08-31 13:30:11, user Ben Sprung wrote:
"In the context of a linear regression, maximizing the variation in the predictor variable will bias the estimated slope downwards, while maximizing the variation in the dependent variable will bias the estimated slope downwards (Hayashi et al. 2018)" -- is one of those two "bias the estimated slope downwards" supposed to read differently, as implied by the "while"?
On 2020-08-31 09:25:55, user Lou Langelier wrote:
Similar behaviour of embryonic cell.<br /> Measles Virus Persistent Infection of Human Induced Pluripotent Stem Cells<br /> https://www.ncbi.nlm.nih.go...
On 2020-08-31 07:45:28, user Evgeny Bobrov wrote:
The article title seems misleading to me. It suggest evidence of how open science practices have controbuted to the COVID-19 response. While some changes due to the pandemic are described, the article does not provide evidence of ways in which open science practices have actually contributed to fighting COVID-19. Rather, the focus is on what has happened so far but did not work, and even more on what could be done in the future. These are very important topics to address, but this is not what the title suggests to me.
On 2020-08-27 13:22:52, user Adrien Lemaignen wrote:
Thank you for this well written article and the proposal to comment it and co-sign. <br /> I agree with the initial statement. <br /> I just have two points to comment considering some proposed solutions:<br /> - data sharing: systematic data sharing does not appear feasible in some situations: anticipated ancillary studies, long-term cohorts etc. <br /> Indeed, the creation and maintenance of a database are costly in time and money. A potential perverse effect of data sharing could be the unauthorized reuse of data by other teams competing with the research team responsible for the original database. A robust safeguard should be guaranteed on this issue.<br /> - limitation of duplicates: an important issue is the low comparability of studies conducted on a same topic. This manuscript could be a good occasion to promote the use of validated international standardized criteria for variable and outcome measurements.
On 2020-08-25 06:54:10, user Heidi Seibold wrote:
Thanks for this nicely written article. I fully agree with the main points and would like to congratulate you on the idea to allow people to co-sign. I think that could send a strong message if enough people co-sign.
There are only two points where I was not fully convinced by your statements, which I'd like to share.
When I started reading the section on expedited reviews, I was surprised by the statement "While faster peer-reviewing does not neccessarily equate with poorer review quality, it remains unclear how thorough the peer-reviewing is [...]" as it suggested that it is probably bad. I had followed Chris Chambers' call for rapid reviews (https://twitter.com/chrisdc... which I felt was a good idea. I still do, but I started to understand that what you mean with "faster" (same or next day acceptance without thorough review) is not the same as what Chambers probably understands as "faster" (thorough yet rapid acceptance of good quality research).
In the section of preprints you metion Twitter as one type of medium (Figure 3). As there exist various bots that automatically tweet about arXiv preprints (https://twitter.com/arxiv_org, https://twitter.com/Brundag..., etc), I wonder if this is at all interesting. I would even assume that both bars could be at 100% as there might be a bot out there tweeting about every arXiv preprint.
Thanks again for the interesting work and good luck with moving the project forward!
On 2020-08-17 21:10:06, user J. Colomb, PhD wrote:
Thank you for writing this. The problems are clearly stated, I am not sure the solution presented are convincing, though. The manuscript may gain if you could analyse the solution a bit more and see when it works, and when it does not, and maybe give some disclaimer on how the "open science" needs to be conducted to achieve these goals, and how this could be monitored?
The "preregistration" solution seem not very convincing to me: If clinical trial (which are preregistered) are not avoiding waste and bad statistical analysis, while do you suggest preregistration in other domains would work? Is there any data on the effect of preregistration in clinical trials?
If we turn the question around: what is missing to preregistration to be actually reaching these goals (without being too much of an administrative burden for the researchers)?<br /> Maybe of interest in this respect: https://www.statnews.com/20...
Similarly, the "open peer review" solution can only be "postulated" to be a solution ? Isn't there any data to back up this claim? What about covid-19 paper that went through open peer review, are they better?
On 2020-08-17 14:08:33, user ricardo wrote:
Hey!, its great to see an article which talk about the issues of open science, bad practices and the misuse of preprints by the media..<br /> Just 2 comments: <br /> Regarding the characterization of the problem in the methodology, do u think could be interesting to add the need to have a defined structure in the methodology that favors reproducibility, for example, using RRIDs, (which will depend on the area and research paradigms)<br /> In the solutions, perhaps also suggest platforms such as Octopus (https://demo.science-octopu...) or hypergraph (https://www.libscie.org/hyp...... as others ways of communicating the research carried out, facilitating suggestions, correct and publish?
On 2020-08-17 13:30:58, user ricardo wrote:
Hey!, its great to see an article which talk about the issues of open science, bad practices and the misuse of preprints by the media..<br /> Just 2 comments: <br /> Regarding the characterization of the problem in the methodology, do u think could be interesting to add the need to have a defined structure in the methodology that favors reproducibility, for example, using RRIDs, (which will depend on the area and research paradigms)<br /> In the solutions, perhaps also suggest platforms such as Octopus (https://demo.science-octopu...) or hypergraph (https://www.libscie.org/hyp...... as others ways of communicating the research carried out, facilitating suggestions, correct and publish?
On 2020-08-30 07:59:11, user Matsuura Laboratory wrote:
Thank you Prof. Jerala for using our ”beta-annulus peptide” for scaffold of vaccine candidate for SARS-CoV-2 !
On 2020-08-30 02:11:32, user Gang wrote:
I read the paper carefully, to my knowledge: <br /> 1. This paper reports sub-pM affinity for a monomeric Nb - 1,000 times than what the previous comment claimed. <br /> 2. They seem to use a novel proteomics approach, where hundreds to thousands of antiviral Nbs were identified, including multiple elite neutralizers that bind many epitopes on RBD.<br /> 3. They tested a set of novel constructs: both heter-dimers and trimers to quench the viral mutation escape.<br /> 4. These are the best biomolecules produced by nature for fighting SARS2. The engineered forms' real effective concentrations are probably much lower than reported/ what they can measure.
Cannot wait to hear their next steps!
On 2020-08-27 06:05:05, user insta gramm wrote:
Good manuscript, but authors cite a recent preprint from Schoof et al. disregarding the fact that they already found nanobodies with sub-nM affinity: https://www.ncbi.nlm.nih.go...
They clearly did the same work here pretty much, and tried to ignore previous efforts to make it look more novel.
On 2020-08-30 00:37:39, user Zdenek Svindrych wrote:
Cool!!<br /> The only slightly confusing thing is the "Mother filament barbed end view" in Fig 3a. I'm no actin expert, but to me it looks like a side-on view of the mother filament. I understand it shows the surface where the "pointed end" of Arp2/3 complex docks onto the filament, but the mother filament should have just one single barbed end (at the barbed end, naturally:-).
On 2020-08-29 21:32:49, user Łukasz Sobala wrote:
This is a very comprehensive phylogenomic analysis of the kingdom of Fungi, the amount of data and work is really impressive. I have a question to the authors about Supplementary Figure S3, where they present the whole tree with the outgroups included. The phylogeny within the outgroups does not correspond to any of the published holozoan phylogenies I have ever come across. With very high support (96%), Capsaspora and Corallochytrium are on the the earliest diverging holozoan branch. Previous analyses (Torruella et al 2012 or Hehenberger et al 2017) pointed to Ichthyosporeans (here represented by: Sphaeroforma, Creolimax, Ichthyophonus, Ichthyosporea sp. XGB 2017a) being less related to animals than Capsaspora or Corallochytrium.
Trichoplax being sister to Nematostella in general emerges in some Dayhoff-6 recoded analyses (Laumer et al 2019 or Laumer et al 2018) in which information is often lost, but is rarely recovered using straight amino acids. It is, however, understandable with so few cnidarian & placozoan species.
The non-animal holozoan taxon sampling is reasonably complete in the outgroup - I wonder then why the authors got a result like this? May there be something wrong with the dataset?
On 2020-08-27 07:22:49, user Sergio Pérez Gorjón wrote:
A great job with new contributions for the establishment of the higher mushroom divisions. Those of us who, like me, have a middle age, and explain mycology to younger people, we find ourselves with the dilemma of where to put the limits to establish the divisions (phyla) of fungi. In recent years, up to 18 divisions have been proposed (Tedersoo et al. 2018) and its usefulness at this level or it is still not clear to me. If, as Phylum, we understand a common strategy, such as the classic Chytridiomycota, Zygomycota, Ascomycota and Basidiomycota, that strategy is still preserved in this work, supported by genetic data. Why not consider Chytridiomycota at the level of a single division, including Monoblepharidomycota and Neocallimastigomycota as well, in a monophyletic group? Why not do the same with Zygomycota by not separating Zoopagomycota and Mucoromycota? Are we not taking the risk of going into monotypic divisions (it is extreme of course)? With my compliments to Authors.
On 2020-08-29 20:48:17, user Manfred Wuhrer wrote:
Interesting to see that the recombinantly produced N protein is glycosylated. However, I doubt that the N protein of the intact virus is likewise glycosylated. I assume that the recombinant N protein is steered to the ER and Golgi explaining its glycosylation. For the N protein produced by the SARS-CoV2 infected cell I expect that it will not enter ER and Golgi but rather dwell in the cytosol upon translation and therefore may lack glycosylation.
On 2020-08-29 15:20:32, user George Munson wrote:
A revised version of this article has been published in Frontiers in Microbiology. https://doi.org/10.3389/fmi...
On 2020-08-29 13:41:50, user Himanshu Singh wrote:
Thank you for a new information regarding the Mtb infections. However, my query is below:
In supplementary Table 6, there is difference between Entities found and Submitted entities found. How the Entities ratio is calculated? For instance in pathway RUNX1 and FOXP3 control the development of regulatory T lymphocytes (Tregs), #Entities Found is 4, and submitted entities found is: 2 (IFNG;IL2RA). Entities ratio: 0.0012.
Please explain.<br /> Thanks<br /> Himanshu<br /> Email: himanshu720@gmail.com
On 2020-08-29 12:20:31, user Bipin Kumar Acharya wrote:
This is very comprehensive piece of writing to describe epidemiological trend and spatial patterns of dengue fever covering entire period of transmission in Nepal. However, I noticed it has ignored previous works (published in SCI indexed journal). These works among several others includes: <br /> Spatiotemporal analysis of dengue fever in Nepal from 2010 to 2014 (https://bmcpublichealth.bio...<br /> “Present and Future of Dengue Fever in Nepal: Mapping Climatic Suitability by Ecological Niche Model (https://www.mdpi.com/1660-4... )<br /> In the last paragraph of this manuscript, authors wrote : “There are no previous studies systematically exploring the epidemiological trend and distribution of the dengue cases in a nationwide scale”. However, above mentioned first article has analyzed spatiotemporal trends and patterns of dengue in Nepal covering 2010-2014. Similarly, the second one has also quantified the potential distribution of dengue suitable areas in Nepal on the context of climate change for the first time. I think previously published relevant research should not missed rather can be discussed as concurrent or against it.
On 2020-08-29 08:39:36, user Alex wrote:
The final article has now been published in Nature Communications. The final authenticated version is available online at: https://dx.doi.org/10.1038/....
On 2020-08-28 14:59:42, user Xuemei Cao wrote:
So many paper about the clear mechanism of antisense of FRQ in Neurospora is clear. It is so bad, the author did not mention that.....
On 2020-08-28 13:55:11, user Wolfgang Wagner wrote:
Dear Readers,<br /> We noticed a mistake in the script for the hemimethylation analysis. In fact, hemimethylation at the culture-associated CpGs was much less pronounced. We have therefore tempered this aspect in a revised manuscript. The title and discussion was changed accordingly. We dearly apologize for this confusion.<br /> Best regards,<br /> Wolfgang Wagner
On 2020-08-28 10:26:15, user Farbod Gh wrote:
The claim made regarding the works cited as 12 a and b is false. <br /> Those examples are not aptamers but rather catalytic DNA and RNA <br /> (Deoxyribozyme and ribozyme) respectively. They make covalent changes to<br /> the target RNA as opposed to aptamers that bind to their target molecule<br /> non-covalently. Please correct that mistake before submission to a <br /> peer-reviewed journal.
On 2020-08-28 08:51:58, user russ Li wrote:
can the authors indicate which suppliers the buffers were obtained from? Suppliers for many of the other reagents/materials were indicated, though.
On 2020-08-28 03:16:36, user Elizabeth Molnar wrote:
This receptor's susceptibility to Ivermectin seems ubiquitous, with multiple CNS/Behavioural effects, perhaps via Catecholamines' actions on purinergic receptors?
On 2020-08-28 00:51:29, user Denzel Zhu wrote:
This was an amazing resource for our project! Making home-brewed kinases and phosphatases via AddGene plasmids that the Chodera lab contributed saved our lab thousands of dollars, compared to purchasing commercial proteins. Our work (1) was built off of the Src and YopH plasmids discussed in this manuscript.
On 2020-08-27 20:26:56, user Jarrett Lebov wrote:
A peer-reviewed version of this article was published in mBio and can be found here: https://doi.org/10.1128/mBi...
On 2020-08-27 18:34:06, user Michael wrote:
Regarding the methods section including image analysis as well as microscopy, may be worth considering https://pubmed.ncbi.nlm.nih...<br /> Guillermo Marqués, Thomas Pengo, Mark A Sanders<br /> Imaging methods are vastly underreported in biomedical research<br /> PMID: 32780019 PMCID: PMC7434332 DOI: 10.7554/eLife.55133
On 2020-08-27 15:55:56, user Laura Harris wrote:
In fact, the GWAS Catalog does now accept direct submissions of unpublished/prepublished GWAS. The submission page can be found here: https://www.ebi.ac.uk/gwas/... and the list of available datasets can be found here: https://www.ebi.ac.uk/gwas/...
On 2020-08-27 15:08:30, user Paul Gordon wrote:
Thanks for posting, very interesting. Do you plan on making the data for these viral genome available via a repository?
On 2020-08-27 13:38:55, user kdrl nakle wrote:
It is funny how a seminal paper by Bette Korber's team got so much flack and now it seems everyone is following their research. Initially some even resisted calling D614G a mutation.
On 2020-08-27 13:07:58, user NagataN_UCD wrote:
Very interesting and informative study. In Exp. 3, what time did you start fasting and gavage oil? I assume the effect of fasting period might be influenced by the diurnal variation of lipid metabolism in mice.
On 2020-08-26 16:46:04, user Jordan Berg wrote:
Metaboverse v0.2.0b is live!<br /> https://github.com/Metabove...
See https://metaboverse.readthe... for a full description of updates.
On 2020-08-26 13:28:16, user Qingtian Guan wrote:
This manuscript is now accepted in the International Journal of Infectious Diseases. We have updated the manuscript in pre-proof format, please refer to the following link for citation for the details: https://www.sciencedirect.c...
On 2020-08-26 08:34:32, user Xiaolong Wang wrote:
In this preprint/manuscript, we present a mechanism of gene repair based on our data and a series of previous studies of others. As a preliminary study, the proposed gene repair mechanism is hypothetical/speculative. Some researchers have sent us many comments, advice, and suggestions. I found that the comments and suggestions are extremely useful. I have written a point-to-point reply to Dr. McMurray’s comments at PubPeer.
By going through hundreds of relevant publications, we found no evidence that is contradictory to this model. So, I am cautiously optimistic that this model is valid, at least partially. At the same time, however, I realized that it is a very complicated problem that needs a series of in-depth studies. We are working on it and will update this manuscript from time to time.
On 2020-08-26 04:26:39, user Elizabeth Molnar wrote:
An important paper which may also elucidate the observed negative correlation between Schizophrenia and Rheumatoid Arthritis, and the positive association of Rheumatoid Arthritis with Bipolar Disorder in women, via the high-lighted gene IDO2.
On 2020-08-25 22:33:59, user Flavio Zolessi wrote:
Revised version provisionally published as a manuscript at the International Journal of Developmental Biology: doi: 10.1387/ijdb.200113fz - http://www.ijdb.ehu.es/web/...
On 2020-08-25 09:05:17, user Mo Li wrote:
This is the published version in Genome Biology: https://rdcu.be/b6q2K
On 2020-08-25 06:14:04, user Patrick Villiger wrote:
This appears to be the first specific approach targeting the SARS-CoV-2. Maybe peptides can be used more broadly in therapeutic developments?
On 2020-08-24 15:35:54, user UAB BPJC wrote:
Review by University of Alabama at Birmingham Bacterial Pathogenesis & Physiology Summer Journal Club:
This paper begins to elucidate the role of GumB, an IgaA ortholog in a S. marcescens rabbit<br /> keratitis model. Overall, we feel this paper is well written and begins to demonstrate the role of GumB on the Rcs system in S. marcescens. We found all experiments to be insightful and straightforward. We especially appreciate the complementation experiments that were performed as we feel these types of experiments are lacking in many animal infection models.
Below are our critiques:<br /> 1. Introducing the roles of wecA and wza in context with the Rcs system sooner in the introduction of the paper would allow us to understand why these mutants were used in early experiments in the manuscript.
More introduction for shlBA would also be useful.
The experiments presented in this manuscript utilize double mutants without single mutant controls. Including these experiments would improve the clarity of the manuscript.
Including a cartoon of the Rcs system and its associated roles along with its regulation by GumB would allow for the reader to understand the system much quicker and easier than what is currently presented.
Throughout the manuscript, many between comparisons are made in the figures that we feel may be unnecessary when there are controls present. Performing more comparisons of mutants to controls may be more informative
On 2020-08-24 15:01:09, user Gary Linz wrote:
OK, I'll start! I recommend that resolution, accuracy and precision be separated into their components. All things being equal, who would want resolution of the different populations? Ah, but all things are not equal. Putting these all under one column is creating the wrong impression. For example, resolving the four equal numbered standards by NFCM is quite impressive for both standards, but if you take a look at the PS mixture, up to a 50% error in size is reported, to go with a "bonus" peak. I am not a big fan of 50% errors. If this system over sizes the bright particles, is it then under sizing the weak scattering EV samples? So here we have an issue with accuracy. When I look at these TEM data I see a lot of 40-60 nm particles, and a significant number of 100 plus nm particles. I can not for the life of me figure out what the nCS1 instrument is measuring to get the highest counts, with all most all between 65-100nm. I have old eyes, so maybe that's it. I will note that the NTA instrument is the only one that measured the larger particles in the EV samples, so another accuracy issue. Regarding precision, it was mentioned that with some measurements it was a challenge to get the same or similar answers three times. This is a precision problem (I am looking at nCS1 data). I would have to look at the complete SOP to determine whether the NTA data could have been improved, but if Min brightness of 30 were used for the EV and/or Si samples, that would explain the missing smaller particles.
The ZetaView instrument will resolve 60nm and 130nm EV in a single sample if run properly, that is the resolution we offer. We would rather measure EV samples correctly than a hard particle mixture that as the authors point out, may not have much baring on EV measurements. Nanoparticles in this size range do scatter to the 6th power, which is a huge issue for dynamic light scattering measurements. It is also a fairly annoying problem for NTA instruments using a 20x objective. I consider it a minor problem for the ZV with a 10x objective. Remember, we are tracking the diffusion of particles, not the light intensity. The table: try as we might, we could not get useful data on the nCS1 under 5e8 particle per ml, let alone 1e7. At higher concentrations we note clogging. The ZV detection range is 1e5 to 1e9, the useful measurement range in my experience is 5e6 to 3e8, sample dependant. These are two different specs and should be reported as such. Size detection limit: I have heard that one of the advantages of the nCS1 is that there is a hard stop at 65nm or 50nm, cartridge dependant. At least in the hand of a novice user, I don't think so. It seems deciding what to include as data and what to omit is quite arbitrary. Perhaps experience is needed (or an orthogonal technique). Now, I have measured reliable down to a 50nm mode on EV samples by scatter, 70nm is very routine. With that in mind, the cut-off for NTA is NOT 70nm. Our size range for EV is 30nm to 1000 nm. We cover this range in a couple of measurements by adjusting camera settings. The nCS1 does their range by using multiple 8-10 dollar cartridges. Sample size: one might get the impression that the ZV requires much more sample that the other platforms, the typical amount of material needed is 2-20 microliters, diluted to 2ml. Time to run a sample; UNC emailed me a couple of weeks ago to say they are running 24-32 samples per hour, versus 2 per hour with their old NS500. Your results may vary. Experience: it matters! Three of these platforms were relatively new to the users, only the nCS1, to my knowledge, was used for an extended period, three years or so? References: any reference about the limitations of NTA using NanoSight instrumentation does not translate to NTA in general. It is largely 8 year old technology. Furthermore, our PMX110 systems with CD camera are not nearly as capable as our CMOS based systems. nanoView and NFCM: I am routing for these companies, as I think they both have potential to add a tremendous amount to this community. I will continue to think the nCS1 is the most dangerous instrument being offered until I'm proven wrong. Conflicts: I built Particle Metrix Inc. in North America, my views are through that lens. I would like to also mention that Michael Pauliatis has a close relationship with Spectradyne, having participated in a promotional webinar and having been given access to experimental cartridges that are not available to the general research community at this time. This is not to say you can not trust what I've written here today, or what Dr Pauliatis has published or presented, just that our thoughts are colored by our associations. Ever the diplomat, Gary
On 2020-08-24 12:11:22, user Sebastian Jaenicke wrote:
This is clearly focused on amplicon sequencing, i.e. metabarcoding, and should not make use of the term "metagenomics".
On 2020-08-24 11:27:31, user Roberto Albanese wrote:
Which GENCODE version was used for the annotation of genes in samples of Series 5 (from GSM4462336 to GSM4462341)? Thank you!
On 2020-08-24 11:07:31, user James Chadwick wrote:
Here is a news about this preprint https://atomstalk.com/news/...
On 2020-08-24 06:40:12, user Emmanuel Odion wrote:
Abstract is not well structured with repetition of words. The title do not match the abstract and the methodology doesn't reflect the study
On 2020-08-23 22:20:03, user Amit Dhingra wrote:
Now published and accessible here:
On 2020-08-23 22:10:32, user kdrl nakle wrote:
Interesting but it would be more interesting with a more common choice of domestic animal.
On 2020-08-23 20:22:08, user Alexis Rohou wrote:
I was asked to review this manuscript for a journal. Below are my comments. I hope they are helpful.
Outcomes of the 2019 EMDataResource model challenge: validation of cryo-EM models at near-atomic resolution
This is a report on the most recent "model challenge", organized in 2019 by EMDR, during which 4 maps obtained from cryoEM datasets were used as targets for atomic model building and refinement. A number of teams submitted models, which were then run through an extensive suite of model validation tools. The study's design, which included three experimental maps of the same target at varying resolutions, made it possible to draw rich conclusions from the comparisons of validation metrics to each other. I found the analysis to be thorough and informative.
This manuscript is a useful historical record of the state of the art in model validation today, a marker of how far the field has come in the last few years, and it makes a number of observations and recommendations that should be of interest to all cryoEM practitioners faced with checking whether the model they are building into their map is as correct as could be. Of course, it will also be of profound interest to those involved in the development of methods for atomic model building, refinement and validation. For these reasons, I should think publication with only minor modifications would be warranted.
One danger with reports emanating from large-scale collaborations between a number of groups is that the text might end up purely descriptive, with any strong conclusions watered down or avoided altogether. This minimizes the potential to ruffle feathers, but also reduces utility to partitioners in the field. This manuscript walks that line pretty skillfully and manages to deliver a few key lessons and recommendations, but I think some sections still skirt around the issues and "just" state observations without delivering as strong a message as they could (or should, in my opinion). Specifically, I thought the sections entitled "Evaluating metrics" at times read like they should have been titled "Describing metric behaviors", because they did not deliver the result of the evaluation, e.g. they avoided clearly stating where some methods have shortcomings and may not be suitable for archive-wide, routine use as robust validation metrics, while other methods checked more of these boxes. In other words, I'd encourage the authors to be more explicitly (self-)critical of the metrics they characterized - what's missing, what can be improved upon?
For example, the Section "Evaluating Metrics: Fit-to-Map" concludes with (p10, l8-10): "Collectively these results reveal that multiple factors such as experimental map resolution, presence of background noise, and density threshold selection can strongly impact Fit-to-Map score values, depending on the chosen metric." I know this will be picked up later in Recommendation 3, but I believe this is the point where you need to say that these are not desirable features in a validation measure to be used archive-wide or for all new depositions (right?).
In this same section:<br /> - p9,l12-13: "The observed trend is expected: by definition each metric assesses a model’s fit to the experimental map in a manner that is sensitive to map resolution." Two things:<br /> 1. I don't recall that, by definition, EMRinger cares about resolution - what I mean is that it's a property of the algorithm that it scores better for high-res maps, but it's not embedded in its definition that it should do so, is it? This is in contrast to map-model FSC which underpins the most-commonly-used definition of cryoEM resolution (Rosenthal & Henderson 2003), and Q score which is defined following a "point resolution"-like metric.<br /> 2. A reasonable outside observer (or at least I) might have had the expectation that the correlation metrics of cluster 1 should also score better as resolution improves... after all, don't we want scores to reward us for higher resolutions and better, more correct interpretations? So why wasn't this expectation also there for cluster 1, and if it was, how about pointing out that the expectation was violated by that cluster?<br /> - Cluster 1: I believe the important thing is here is that these are real-space, not frequency-normalized, correlation scores. I suggest changing "The cluster consists of six correlation measures" to "The cluster consists of six real-space correlation measures"<br /> - p9, l7-9: "The observed trend arises at least in part because as map resolution increases, the level of detail that a model<br /> map must faithfully replicate in order to achieve a high correlation score must also increase." Presumably, one important factor is the resolution at which the model-maps are generated. If the model-maps were generated at, say, 1.2 Å resolution, one might expect the opposite trend in real-space correlation scores: the score should increase as the resolution improves and approaches 1.2. Is there something that can be stated briefly about what resolution these methods generate their model-maps? Also, as I said above, doesn't this seem like the "wrong" behavior? Shouldn't validation metrics give better score for higher resolutions? If not, perhaps explain why, but if so, I think it is worth stating that this is not a desirable property.
Separately:<br /> - p10, l19-20: I have a question, to which I am not sure an answer exists. Is the fact that 33 of the submitted models have zero outliers expected (statistically speaking) given the resolution range? In other words, what's the p-value of this occurring? On a very naive level, I bet this would be highly unlikely unless Rama restraints were used. Can the authors make any statements about this, e.g. "more than half of submitted models had zero Rama outliers, which would be extremely unlikely in the absence of restraints used during refinement".<br /> -p 10, l21-22: Would the authors be comfortable adding a statement along the lines of, "and the reduced utility of Rama outliers as a validation metric" at the end of the paragraph? I just think we could do with reviewers and the field in general acknowledging that zero Rama outliers is actually weird, not expected, and not a sign of truly improved models.<br /> - p12, l9-11: "A wide variety (...) in different places". Please re-check this sentence. Is it missing "were used to produce a model"?
-p 5, l16: perhaps "derived" -> "convened" ?
My suggestion: could the authors add a figure depicting the geometry of a problematic bond, perhaps next to the Rama-refined (wrong) version as well as the flipped and corrected version of the geometry? Whatever might be the most simplified depiction of this, I would suggest without an experimental mesh, and erring toward the abstract, rather than realistic.
p32, l27-28: "but to the same cluster in b" - that isn't saying anything, is it? since, all measures were in the same, and only, cluster...
Figure 4 - I suggest a few tweaks to improve intelligibility on first read:<br /> -- label panels a and b to differentiate them, e.g. "a - per-model correlation", "b - per-target correlation"<br /> -- label the clusters "c1", "c2", "c3" rather than 1,2,3<br /> -- panel c: It's not obvious at first glance that 1,2,3 in c refer to 1,2,3 in a. Switching to c1,c2,c3 notation may help, but also how about framing them in red like they were in panel a, rather than black?
Alexis Rohou<br /> 23-Aug-2020
On 2020-08-23 18:48:11, user Shahar Sukenik wrote:
All code used to produce the main and SI figures is now available at https://github.com/sukenikl...
On 2020-08-20 20:40:34, user harvardbmw wrote:
Why is the Methods section missing?! Should we start publishing preprints that have just a title?
On 2020-08-23 17:43:15, user Sourbh Garg wrote:
Troxerutin blocks the Complement Component 9 and save the cells from the process of necrosis.
On 2020-08-23 00:18:40, user Lim Heo wrote:
Interesting study!! Is it possible to or how about embedding antibody structures and their sequences simultaneously? If it is possible, then I think it does not necessary to generate sequences via Rosetta FastDesign, and the model can directly generate from the model. The model may learn sequence-structure relationship.
On 2020-08-12 15:23:12, user Debora Marks wrote:
Seems like a great paper Po-Ssu; Worth mentioning other generative models of proteins? Riesselman (VAE, Nature Methods 2018) and Riesselman (generate antibodies 2019)<br /> https://www.biorxiv.org/con...<br /> Oh – and the first paper on folding from coevolution – try 2011 PLoS One Marks et al <br /> In any case we’d love someone from your lab would do a journal club for us?
On 2020-08-12 00:20:35, user Debora Marks wrote:
Seems like a great paper Po-Ssu; Worth mentioning other generative models of proteins? Riesselman (VAE, Nature Methods 2018) and Riesselman (generate antibodies 2019)<br /> https://www.biorxiv.org/con.... Oh – and perhaps where you mention folding from coevolution – try the first paper Marks PLoS One 2011.<br /> In any case we’d love someone from your lab would do a journal club for us -would be fun!
On 2020-08-22 08:37:43, user michael.m.laue@googlemail.com wrote:
We will upload a revised version considering the recently published work of Turoňová et al. and two preprints (https://doi.org/10.1101/202... https://doi.org/10.1101/202... as soon as possible.
On 2020-08-21 22:59:19, user aspiringscientist wrote:
Supplementary information is not accessible
On 2020-08-21 21:27:05, user Doo Bilzarain wrote:
what where the RMT/ <br /> breathing techniques used in the study are where can one find them?
On 2020-08-21 20:01:35, user Carmen Gu Liu wrote:
Dear readers, this paper was accepted in mBio. To access the final published version, which has the most updated text and figures, please visit: https://mbio.asm.org/conten...
On 2020-08-21 19:34:36, user Enrique Medina-Acosta wrote:
Please follow the comment posted by Borsa, M., and Mazet, J.M. (2020). Attacking the defence: SARS-CoV-2 can infect immune cells. Nature Reviews Immunology doi: 10.1038/s41577-020-00439-1: "As monocytes and lymphocytes do not express ACE2, it remains to be seen whether the virus uses an alternative entry strategy and whether circulating infected immune cells contribute to viral spread and COVID-19 disease progression."
On 2020-08-10 08:01:08, user OxImmuno Literature Initiative wrote:
On 2020-08-21 15:31:37, user Maël BESSAUD wrote:
I do not understand why you did not consider all the enterovirus serotypes available. Which simian enteroviruses did you use in Figure 3? Do simian enteroviruses of species EV-A, EV-B, cluster with simian enteroviruses of species EV-J or EV-H or do they cluster with human EV-As and EV-Bs?
On 2020-08-20 20:57:15, user Shashank Patel wrote:
Nice study. An indepth followup from our early study in melanoma.
On 2020-08-20 19:59:26, user hansdb wrote:
Hello,
Reading the preprint made me very curious about the Y-haplogroup of the I2 sample that is described. To me it looks a very likely I-S2525 candidate (=I2a1b2), as is the Contineza sample R11.
I-S2525 aka I2a1b2 (and its subclades I-S2519 and I-S2497) is a a Y-DNA haplogroup that is longtime overlooked and now pops-up regularly in European aDNA research:
Haplogroup I-S2519 (FTDNA and YFull)<br /> • PER3123 Ancient genomes from present-day France unveil 7,000 years of its demographic history (Brunel 2020);<br /> • SRA62 Sramore, Leitrim, Ireland - Mesolithic 4226-3963 cal BC (Cassidy 2020);<br /> • R11 Ancient Rome: A genetic crossroads of Europe and the Mediterranean (Antonio 2019).
Haplogroup I-S2497 (FTDNA) / I-S2524 (YFull)<br /> • I6767 Cheddar_man from Gough’s Cave, Cheddar Gorge, Somerset, England - 8607-7982 cal. BCE (Brace 2019);<br /> • SUC009 Su Crucifissu Mannu, t.22, Porto Torres, SAS, Sardinia - EBA 3808-3612 BP (Marcus 2020).
Best wishes,
Hans De Beule, Belgium<br /> Citizen scientist focusing on I-S2525 branches
On 2020-08-20 19:12:48, user Kausik Bhattacharyya wrote:
https://bmcmicrobiol.biomed...<br /> link to the article
On 2020-08-20 18:31:24, user marc verhaegen wrote:
There's no doubt any more: australopiths were not cursorial, but were wading-climbing hominids in flooded or swamp forests, much like bonobos and lowland gorillas wading bipedally in forest swamps. For an update, google "Lucy was no human ancestor 2020 PPT Verhaegen".
On 2020-08-20 15:28:48, user Yina Du wrote:
Please welcome to checkout our featured toolset "Lung at a glance" ( https://research.cchmc.org/... ). Or stop by LGEA Web Portal (https://research.cchmc.org/... ) for more exploration!
On 2020-08-20 08:37:54, user Yannick Wurm wrote:
Heads up that this is now published at eLife<br /> https://doi.org/10.7554/eLi... - huge thanks to the reviewers and editors who helped improve the ms.
On 2020-08-20 04:08:47, user Souvik Bhattacharyya wrote:
Please read the peer-reviewed version of this manuscript here in Nature Communications: <br /> https://www.nature.com/arti...
On 2020-08-20 03:20:20, user Joshua Mylne wrote:
This work is now published in Journal of Biological Chemistry, see https://www.jbc.org/content...
DOI 10.1074/jbc.RA120.014781
On 2020-08-19 18:06:32, user Jeremy Horst wrote:
Published here:<br /> ingentaconnect.com/content/...
On 2020-08-19 15:28:27, user cleverThylacine wrote:
What I think is really interesting about this is whether or not it would affect other coronaviruses.
While SARS-CoV-2 is killing a lot of people right now, disrupting world economies, and forcing people to live in an unnatural manner that's not psychologically healthy to protect themselves (I don't know about you, but I miss hugs), and is also affecting felines of all sizes in human care, there are an awful lot of coronaviral diseases.
Some of them, like SARS and MERS, are also deadly.
But the common cold is also a family of coronaviruses that causes a lot of misery and lost productivity. Nonhuman animal diseases like feline infectious peritonitis (also a coronavirus) kill pets and cause misery both for pets and the people who own them.
If these coronaviral spikes are also affected--and if the coronaviral spikes of other viruses that have not yet made the leap to humans are affected--and the preparation does not lose its efficiency--this could really make a lot of lives, not all of them human, immensely better. Especially given the number of secondary bacterial infections that follow colds in people, for which our treatments are not what they once were.
On 2020-08-18 00:01:03, user Vivian Siegel wrote:
Is there a chance this could get through human trials and be deployed quickly? They talk about it as a "stop gap" before a vaccine, but how much before a vaccine would it be ready?
On 2020-08-12 14:07:52, user bjh55 wrote:
These nanobodies are interesting, but this must be tested in a living biological system. I can find nothing about their toxicities. This has a very long way to go yet.
On 2020-08-12 02:41:52, user Alexander Stollznow wrote:
Good luck with this, and hopefully a range of prophylactics and therapies will all become available in a hurry, and soon.
On 2020-08-19 12:37:40, user Tomáš Hluska wrote:
Hi, if you have still chance to change the manuscript, here are a couple of things I noticed:<br /> - p. 7 at the very end sentence starting "Compared to wild type" contains twice the concentrations<br /> - p. 9 first line - should be Suppl. Fig. 4B<br /> - You don't use consistently the abbreviations. Mostly, you use LOT, but e.g. in Fig. 6 description you use KO.<br /> - Fig. 7 - what are the standard conditions? Are they the same for both transporters or do they differ? BTW in the text you say (and I would agree) that the Ade uptake decreases in absence of E source, while in the Fig description you say "its activity is independent of an energy source.". Yeah, it may be less affected but there is still some effect.<br /> p. 15 - may transports - should be may transport
Honestly, I don't see much difference in the azg2 ko and AZG2 OE plants on 8-aza-Ade (Suppl. Fig. 4B).
On 2020-08-19 00:56:10, user Voice of Reason wrote:
Pitching this to Trump is all about getting publicity and raising investment money. Oleandrin is known to be highly toxic in animals and humans.
On 2020-08-18 19:24:55, user bfoster68 wrote:
This was done in a lab, not on animal or human subjects. It isn't a cure and the FDA is not going to approve it without extensive studies showing it's efficacy
On 2020-08-17 19:36:49, user Felix Schweizer wrote:
The study reports on an experiment that was done once in triplicate. In 'supplementary figures' the study was repeated once more. The data thus reports on two repetitions (n=2). This falls short of basic scientific standards. <br /> Interestingly, two of the authors are directly involved in Phoenix Biotechnology (as disclosed), a company that hopes to commercialize an oleander extract....
On 2020-08-17 04:59:14, user Asher A. Miller wrote:
Given the desperation of people at the moment, I would like to point out that this paper says the compound does not have an effect below 0.05 ug/mL. The compound’s lethal dose has been estimated to be 0.02 ug/mL.
On 2020-08-18 19:59:49, user Arie Horowitz wrote:
I encourage readers to suggest references we may have missed on proteomics of human CSF, while the resubmitted manuscript is undergoing external review.
On 2020-08-18 19:12:57, user Rafael Feras UFCG odontologia wrote:
Great article. About Figure 1, I can't see the letter "D" in the figure!
On 2020-08-18 16:43:53, user D.M. wrote:
Relevant comparisons to other promising vaccine modalities may help this approach, stated as translational by the authors, to be evaluated in the acute global need for a vaccine platform.
On 2020-08-18 16:24:13, user Zhijie wrote:
Now available in PNAS: https://www.pnas.org/conten...
On 2020-08-18 08:55:53, user Guillaume van Niel wrote:
A very interesting study that nicely completes former studies on distinct populations of EVs secreted by the epithelial cell lines HT29 and T84 (van Niel et al Gastroenterology 2001).
On 2020-08-18 06:20:49, user Yishai wrote:
Unfortunately, this paper's claim seems to be an artifact. We have used the protocol described and indeed get similar-looking cells. However, RNA-seq revealed that they were, in no way, neuronal cells - rather than remained monocytes.
On 2020-08-18 03:42:43, user Lin Sonyan wrote:
How long does this gel remain attached to the nasal mucosa? I guess it needs to remain so for at least a few hours to be effective.
On 2020-08-18 03:35:56, user Ming-Jiun Yu wrote:
Great work! This distills potential kinases for aquaporin-2 phosphorylation. Knowing where aquaporin-2 is phosphorylated and dephosphorylated may further pin down the kinases and phosphatases. https://pubmed.ncbi.nlm.nih...
On 2020-08-18 03:16:44, user Jink wrote:
Where can I get the codes? I want to try it..!!
On 2020-08-17 22:57:15, user Aline Maria da Silva wrote:
Dr. Kuehn, congratulations on the manuscript "Protective Plant Immune Responses are Elicited by Bacterial Outer Membrane Vesicles". We were very pleased to see our work cited on line 70 (Ionescu et al., 2014), however we call your attention that it does not involve a marine organism, but instead a plant pathogen. An example editing could be "The sheer abundance of bacteria suggests that OMVs could have major roles in different ecosystems, and already researchers have started to reveal their potential contributions in the marine environment (Biller et al., 2014, Biller et al., 2017, Bahar et al., 2016), and plant pathosystems (Ionescu et al., 2014)."<br /> We wish you success with the publication.<br /> Aline
On 2020-08-17 18:59:05, user OxImmuno Literature Initiative wrote:
On 2020-08-17 18:53:09, user OxImmuno Literature Initiative wrote:
On 2020-08-17 18:48:22, user Kenny Day wrote:
It sounds and looks like a fantastic program, but have yet to get it to work.
On 2020-08-17 18:28:45, user OxImmuno Literature Initiative wrote:
On 2020-08-17 18:26:22, user OxImmuno Literature Initiative wrote:
On 2020-08-17 18:22:11, user OxImmuno Literature Initiative wrote:
On 2020-08-17 18:11:34, user OxImmuno Literature Initiative wrote:
On 2020-08-17 18:07:49, user OxImmuno Literature Initiative wrote:
On 2020-08-17 18:04:46, user OxImmuno Literature Initiative wrote:
On 2020-08-15 01:19:34, user leon islas wrote:
Great work. Small detail on line 452: "implicaitons for host-direc ted", should be "implications for host-directed"
On 2020-08-17 09:48:06, user Russ Gray wrote:
Link to the published manuscript in Scientometrics
On 2020-08-17 07:54:36, user Andrea Zaliani wrote:
Sirs<br /> I have problem with your definition of synergy. HSA should be positive for synergy and should use the max activity of single components alone, not the minimum. At least so, is here described https://bpspubs.onlinelibra....<br /> Am I wrong?<br /> Best<br /> Andrea Zaliani
On 2020-08-17 07:32:54, user Paniz Farshadyeganeh wrote:
Dear Authors,
I could not find any link to supplementary data. I would like to know if it is possible to have it?
Bests,<br /> Paniz
On 2020-08-17 01:50:52, user Thomas-nick wrote:
it is scary to think that marine species may be affected, especially shoreline and those exposed to raw sewage. Authors should extend these important findings with in vitro data. However, I doubt that many of these species have cell lines for in vitro infection data (even less likely that lung lines are available).
On 2020-08-17 01:43:16, user Fhff_small wrote:
Interesting article. It brings up a lot of relevant discussion about previous pandemic viruses spilling over to other species. Risk assessment is important for biological conservation.
On 2020-08-15 10:44:11, user kdrl nakle wrote:
It would be nice to have some data or at least some data in relation to other transmissible diseases in marine mammals but there is nothing like that. This is more of an article for science mag than for scientific journal.
On 2020-08-16 15:26:56, user SW wrote:
I keep coming back to this wonderful paper, and I hope that these methods can be used to analyze more COVID-19 patients! One question: for donor M, if you look at the "pre-existing SARS-CoV-2-reactive CD4+ clones in the CM subpopulation 1 year before the infection," how big of a role do they play in the response to SARS-CoV-2? What fraction of responding CD4+ cells are derived from this (presumably cross-reactive) memory population? I am trying to get a sense for whether these preexisting memory cells were very important in fighting off the infection or whether they were just some small fraction of the overall response. Thank you.
On 2020-08-15 23:26:06, user Peng He wrote:
It seems that the html format is massed up. But please check out the pdf which should be intact! And of course the paper is now officially online
On 2020-08-15 09:26:51, user Li Cai Chen wrote:
Indeed I saw exciting presentation by Dr Berger in free webinar already in July ! On Bristol team discovery of druggable pocket in SARS-CoV-2 and hopefully approach like Dr Rossmann did. Why Bristol team work not cited and discussed in detail in this manuscript here https://www.biorxiv.org/con... ?
On 2020-08-14 08:59:51, user sathish Yadav wrote:
Hi, The FA binding pocket of SARS-CoV2 is already shown and find the link bellow. <br /> https://www.biorxiv.org/con....
On 2020-08-14 07:27:43, user Kapil Gupta wrote:
It seems authors might have missed our paper. We already published same findings 2 months ago. We even have shown more experiments to further identify the lipid there and also activity assays of lipid bound spike.
Here is link for our paper.<br /> https://www.biorxiv.org/con...
On 2020-08-14 06:05:55, user Imre Berger wrote:
This finding has already been published previously in June.<br /> See publication Toelzer et al "Unexpected free fatty acid binding pocket in the cryo-EM structure of SARS-CoV-2 Spike protein". <br /> https://www.biorxiv.org/con...<br /> Please cite and discuss in your manuscript.
On 2020-08-14 05:37:44, user Christiane Schaffitzel wrote:
Dear David, please note that we have published this already two months ago: Toelzer et al. <br /> Unexpected free fatty acid binding pocket in the cryo-EM structure of SARS-CoV-2 spike protein. doi: https://doi.org/10.1101/202....<br /> Please cite and discuss our paper in your contribution.
On 2020-08-15 08:55:36, user 柊元 巌 wrote:
Thanks for using our sequence data. The accession numbers starting from LC and AB are all from Japan. Best regards<br /> Iwao Kukimoto
On 2020-08-14 22:38:02, user Vectorman wrote:
This is a very interesting article and a promising approach. However, the authors should more directly acknowledge prior work on this concept. They cite a Nature Communications manuscript by Maselko et al. yet do not mention that it was a demonstration of the same idea. A Scientific Reports manuscript by Waters et al. is also cited but it is once again not acknowledged that those researchers were working on the very same approach.
Furthermore, the authors should be aware that there is a Maselko et al. bioRxiv preprint (link below) that has demonstrated 100% reproductive isolation in D. melanogaster using this same mechanism which was posted in April 2020 and should be cited if the current work is published in a journal that accepts preprint citations.
On 2020-08-14 16:52:48, user Phillip Morin wrote:
Glad to see more robust testing of PSMC parameters! I have several question. 1) For Figure S4, is this showing masking of regions with <10x, <20x, <30x, etc. coverage? It looks like the average coverage for this genome was ~45x (based on 50% masked falling between 40x and 50x coverage). How does this reflect higher coverage of repeat regions? Masking regions with >2x average coverage is typically how repeat regions are removed in unmasked genomes, so in this case, regions with >90x coverage masked would be of interest to see how it affects PSMC of genome that is not repeat masked (compared to just using a repeat-masked genome).<br /> Also, the effects of altering -r (Figure S6) and -t (Figure 4a) are interesting, but it's unclear how an optimal value is obtained. What metrics are used to determine what combination of values is optimal?
On 2020-08-14 13:16:31, user GraemeTLloyd wrote:
Hi Jorge. FYI, Claddis now performs AIC tests with the (renamed) Claddis::test_rates() function and these are likely preferable to an LRT. (Try installing version 0.6.0 from GitHub if you want to play with this.)
On 2020-08-14 12:26:01, user samer singh wrote:
The article is in press with details as under:
Kaur R, Tiwari A, Manish M, Maurya IK, Bhatnagar R, Singh S. Common Garlic (Allium sativum L.) has Potent Anti-Bacillus anthracis Activity. J Ethnopharmacol. 2020 (in Press). PII:S0378-8741(20)33112-3
On 2020-08-14 09:30:03, user Jens Staal wrote:
Accepted version:
On 2020-08-14 08:52:19, user Min Hooi Yong wrote:
This article has now been published in PLOS ONE <br /> doi: 10.1371/journal.pone.0219233
On 2020-08-14 08:33:30, user Matthew Templeton wrote:
Interesting paper, it would be good to compare expression in apoplast-like conditions to what we found in planta (McAtee, P. A., et al. (2018). "Re-programming of Pseudomonas syringae pv. actinidiae gene expression during early stages of infection of kiwifruit." BMC Genomics 19(1): 822.)
On 2020-08-14 07:09:41, user Helene Banoun wrote:
I am very interested in your work : I published a hypothesis to explain the decline of the epidemic based on the evolution of the virus against the immune system of its host : EVOLUTION OF SARS-COV-2 IN RELATION TO THE HOST IMMUNE SYSTEM. <br /> http://ssrn.com/abstract=3637909 DOI: 10.2139/ssrn.3637909
I am not an expert in any of the fields I cover (virology, immunology, biological evolution) but I do try to have a multidisciplinary approach.
In your recent article I understood that regions involved in virus-host interaction show an excess of mutations. On the other hand the regions responsible for the synthesis of RdRp are more conserved.
However, on https://covid19.galaxyproject.org/evolution/ , I see that the most interesting site of mutations with evolutionary meaning is on the RdRp. Is this a contradiction or did I misunderstand? There are few mutations on RdRp but they are important from an evolutionary point of view?
Concerning the interpretation of the temporal evolution of the composition of RdRp and Orf30/57, I have a question: the curves seem to overlap with the pandemic (beginning of February and attenuation at the end of April). Can this be interpreted as an argument to point to the evolution of the virus against the immune system as the main variable responsible for the evolution of the pandemic?
In particular for the RdRp, the passage from variant P to variant L: a mutation would have allowed the virus to increase its replication speed and therefore its virulence, then another mutation would have made it more benign? Similarly for variant Q of Orf3a/57: its appearance and then disappearance could correspond to a stronger capacity of the virus to make the immune system react and therefore lead to the immunopathological phenomena responsible for severe Covid?
Thank you for your attention!
Hélène Banoun,
On 2020-08-14 06:18:38, user Ken wrote:
This paper is now published in PLOS ONE <br /> Kyoda K, Ho KHL, Tohsato Y, Itoga H, Onami S (2020) BD5: An open HDF5-based data format to represent quantitative biological dynamics data. PLoS ONE 15(8): e0237468. https://doi.org/10.1371/jou...
On 2020-08-14 00:10:44, user C'est la même wrote:
While the authors have focused their results on the suggestion that heparin is a potential treatment, there also remains the possibility that proteoglycan dysregulation plays a role in the pathology of COVID-19 and potentially plays a role in "longcovid" too.
On 2020-08-14 00:05:28, user Joseph Miano wrote:
Very nice preprint! We have been working on this since last November and will be presenting our latest findings of perfect Prime editing in mice at CSHL next week. As with any mouse zygote injection, targeting and repair outcomes are highly locus dependent.
On 2020-08-13 12:25:42, user kdrl nakle wrote:
That will too complex and too complicated to treat people that are days away from dying. It is OK for cancer but I bet it is not going to work effectively for acute infections. It is interesting so try to prove me wrong.
On 2020-08-13 12:16:22, user kdrl nakle wrote:
Perhaps you should test it first in-vitro on a live virus to see whether it really does inhibit replication. There are so many various claimed inhibitors of this or that and nothing yet available for a real therapy. I am weary of these researches that are leaving real test to others, too many of them don't go anywhere.
On 2020-08-13 12:06:59, user kdrl nakle wrote:
It would be great if you would have any real manufacturing support.
On 2020-08-13 09:54:28, user Martin R. Smith wrote:
Sounds like a promising framework – great that your analyses seem to indicate strong performance.<br /> Have you also considered how the precision of CellPhy results compares to those of the other methods you examine? It would be worth ruling out the possibility that the increased accuracy that you observe is simply a result of reduced precision (see Smith 2019, Biology Letters).<br /> To avoid the various biases that plague the RF distance, I also wonder whether there's an argument for using a method that offers a more complete picture of tree distance (e.g. those reviewed in Smith 2020, Bioinformatics) – information theoretic distances are probably better suited to evaluating the performance of methods against a simulated reference tree, and can be normalized in a more natural way. Indeed, I couldn't see whether you normalize the RF distance with respect to the total number of splits in the "true" and reconstructed tree, or the reconstructed tree only, which would have a significant effect on the values recovered.
On 2020-08-13 08:50:09, user Martin R. Smith wrote:
I'm very interested in attempts to quantify the amount of phylogenetic signal within datasets, and this is a very nice contribution to this subject – congratulations. It is perhaps a little surprising that the difference between low and high quality datasets, though clearly evident, is not even more prominent in Fig. 6. Have you considered supplementing your Robinson-Foulds analysis with more sensitive metrics that are slightly less binary? RF treats partitions as either present or absent, leading to various problems, not least that it can miss partitions that are 'almost' right. I wonder whether information theoretic distance metrics (Smith 2020, Bioinformatics; see R package 'TreeDist') might show an even clearer distinction between trees inferred from low-quality and high-quality datasets?
On 2020-08-13 08:23:35, user Martin R. Smith wrote:
This is an interesting study and a promising approach. <br /> My one question would be whether the Robinson-Foulds distance is the most suitable measure of tree distance on which to base the linkage ratio. The RF distance suffers from a number of shortcomings, many of which are exacerbated when pectinate (i.e. fully unbalanced) trees are involved, as moves of a single leaf can 'knock out' a disproportionately large number of splits – so it might have particular scope to produce misleading results in the examples that you have used.<br /> I've reviewed some possible alternatives in Smith (2020), Bioinformatics, doi:10.1093/bioinformatics/btaa614 , and fast implementations are available in my R package 'TreeDist' – though unfortunately I don't yet have a python front end to the underlying C++ code. The quartet distance might be particularly relevant, as the distance between two entirely random trees takes a constant value (1/3) – would this obviate the need to generate unliked topologies in order to normalize the linkage ratio?
On 2020-08-13 06:05:21, user Sarah M wrote:
Response to Etebari et al. 2020 ‘Genetic structure of the coconut rhinoceros beetle (Oryctes rhinoceros) population and the incidence of its biocontrol agents (Oryctes rhinoceros nudivirus) in the South Pacific Islands’ bioRxiv preprint doi: https://doi.org/10.1101/202...
Sean D.G. Marshall, Sarah Mansfield, Trevor A. Jackson <br /> AgResearch, Lincoln Science Centre, Private Bag 4749, Christchurch 8140, New Zealand
Kayvan Etebari and co-authors present genetic data that they contend supports their claims that the recent invasion of coconut rhinoceros beetle (CRB) into new areas of the Pacific was not caused by CRB-G (Marshall et al. 2017). Instead, they argue this invasion process is driven by several genetically distinct groups of CRB. A central plank to their argument is genetic analysis of the invasive CRB population found on Guadalcanal, Solomon Islands. They also present data from several countries on infection rates in CRB populations of the Oryctes rhinoceros nudivirus (OrNV) and hypothesise that OrNV has entered the invaded countries along with the invasive CRB population.
We have serious concerns regarding the methodology used to analyse the data presented by Etebari et al., and their interpretation of the results. Previous attempts to raise these concerns with the lead author and to invite discussion of the findings with the CRB Action Group have been unsuccessful. As it stands, the preprint omits significant methodological information and fails to place their findings in the wider context of CRB invasion into the Pacific. Our concerns can be grouped under three key areas: 1) conflation of two different levels of population structure within CRB, i.e. biotype and haplotype; 2) recent research to address new CRB invasions is not taken into account, particularly in Vanuatu and the Solomon Islands; and 3) failure to prevent cross-contamination leading to artificially high ‘rates of OrNV infection’, which are not substantiated by other published techniques used to detect OrNV infection in CRB.
Below we elaborate on these three points. We invite the authors to contact us directly regarding the concerns raised.
1) conflation of two different levels of population structure within CRB: biotype and haplotype<br /> Marshall et al. 2017 presented genetic data that characterised different populations from the native and invasive range of CRB. In doing so, they identified a genetic marker that distinguished the newly invasive populations from older populations that arose from the initial Pacific invasion by CRB. They also presented bioassay data demonstrating that the new invasive CRB populations were not susceptible to infection by ingestion of the original strain of OrNV that was used to control the initial Pacific invasion of CRB (Huger 2005). Ingestion is the natural route of infection for OrNV so inability to infect new invasive populations is a serious concern for control of CRB. They concluded that there were four clades within the CRB populations they had sampled, with some further subdivision within each of these clades (Fig. 2, Marshall et al. 2017). Three of these clades, while genetically distinct, were all characterised by their susceptibility to the original strain of OrNV used to control the initial CRB invasion in the Pacific. These three clades included native CRB populations and populations from regions affected by the initial CRB invasion and collectively were named CRB-S. The fourth clade included CRB populations from the newly invaded regions (Guam, Papua New Guinea, Hawaii, Solomon Islands) as well as parts of the native range (Philippines, Indonesia). This fourth clade was named CRB-G. Thus, Marshall and co-authors identified two distinct levels of population structure within CRB. The first level (CRB-G and CRB-S) is associated with susceptibility to the original strain of OrNV introduced to the Pacific. The second, more complex, level reflects geographic groupings in the native and invasive range of CRB.
Reil et al. 2018 built on this initial analysis of CRB genetics by investigating the genetic substructure of CRB in more depth, particularly in Palau, where there may have been multiple CRB invasions. They concurred that the new Pacific invasion was correlated with the presence of CRB-G. A key outcome of their paper was the use of the term ‘biotype’, i.e. conspecifics that appear similar but exhibit variation in one or more functional traits, to characterise the CRB-S/CRB-G dichotomy. This is a useful distinction to avoid confusion between this level of population structure, and the more finely divided population structure and haplotypes associated with different geographic regions.
Etebari et al. conflate these two levels of population structure by inserting the PNG haplotype group into the CRB-S/CRB-G dichotomy. A PNG haplotype was identified by Marshall et al. 2017 and placed in Clade II, among the three clades associated with CRB-S. These specimens came from several locations in PNG known to have been affected by the earlier Pacific CRB invasions in the 1940s (Table 2, Marshall et al. 2017). The CRB-G specimens from PNG were collected solely from Port Moresby, which is presumed to be the original invasion site for CRB-G within PNG. In the Solomon Islands, CRB-G was first identified in 2015, and all field collected samples included in the analysis presented by Marshall et al. 2017 were CRB-G. We do not dispute that Etebari et al. have found CRB individuals with the PNG haplotype on Guadalcanal, but we do not support their claim that this is evidence for a separate wave of invasion into the region (see next section for further discussion).
2) recent research to address new CRB invasions, particularly in Vanuatu and the Solomon Islands <br /> Etebari et al. report the presence of OrNV in CRB-S beetles collected from Efate, Vanuatu at some point between January and October 2019, but neither collection date nor specific locality are provided. These details are important because the presence of CRB-S was only confirmed in Vanuatu during June 2019. Our CRB-S samples collected from Mangaliliu, Efate, between June and September 2019 are negative for OrNV. In mid-September 2019, as part of the local eradication efforts against CRB, live OrNV was imported into Vanuatu. Bioassays were conducted to assess virus activity against the invasive CRB-S population and planned releases of OrNV were made on Efate in 2019 (Biosecurity Vanuatu, pers. comm.). Prior to the release of this preprint, we were unaware that these research activities in Vanuatu were likely to affect the conclusions drawn by Etebari and co-authors.
Etebari et al. also report the presence of CRB-S and the presence of OrNV on Guadalcanal, Solomon Islands in 2019. The sampling period is stated as between January and October 2019, but again neither collection date nor specific locality are provided. The authors state that ‘the OrNV now infecting O. rhinoceros in Solomon Islands arrived with an incursion of infected O. rhinoceros that originated in Southeast Asia’. We do not dispute the presence of CRB-S in the wider Honiara region of Guadalcanal in 2019, nor do we dispute the presence of virus in the same location and at the same time, because we have independent samples that confirm their presence in Honiara in 2019. There is, however, a simpler explanation for these findings. As part of the response to the CRB-G invasion into Honiara, screening of imported live OrNV isolates for virulence against CRB-G began in Honiara during 2016 (Marshall 2016). At the same time, CRB-S beetles were brought to Honiara from the Shortland Islands (Western Province, Solomon Islands) as part of the same project. There have been subsequent imports of live OrNV to Honiara for research purposes at intervals since 2016. It is likely that the presence of CRB-S and OrNV in Honiara is due to accidental release into the local environment. This does not support the invasion hypothesis suggested by Etebari and co-authors.
Furthermore, we note that our CRB samples from Russell Island (n = 3, Sept. 2019; n = 13, Feb. 2020; AgResearch 2020) were negative for OrNV, in contradiction to the results presented by Etebari et al. We concur with Etebari et al. that CRB populations in the New Georgia island group are negative for OrNV.
We agree with Etebari et al. that the effect of interbreeding between CRB-S and CRB-G on OrNV susceptibility requires further investigation, particularly in Honiara, where the two biotypes now occur together outside of their native range. Care needs to be taken, however, in the assessment of OrNV infection rates (see next section).
3) failure to prevent cross-contamination leading to artificially high ‘rates of OrNV infection’<br /> Etebari et al. present evidence of OrNV infection rates (%) based solely on PCR analysis of gut tissue samples. These tissue samples came from adult beetles captured in pheromone traps. From the information presented in the methods, it is unclear if sufficient precautions were taken to prevent accidental cross-contamination between beetles during the trapping process because the trap locations, length of time between trap set up and beetle collection, and beetle handling after collection are not described adequately. If an OrNV infected beetle is present in a trap among uninfected beetles, virus particles are easily transferred between individuals. This problem was documented by Ramle et al. 2005, who recommended careful handling of trapped beetles as a first step to minimise contamination risk. A tweet from the lead author of this preprint, dated 9 April 2019, includes a photo that shows strong potential for cross-contamination between beetles.
It is also unclear if the PCR protocol used by Etebari et al. included an appropriate dilution step to further reduce the risk of false positives because no details of the protocol are presented. Marshall et al. 2017 recommended a 1 in 5000 dilution to improve the accuracy of OrNV detection using PCR. Furthermore, care needs to be taken to avoid accidental contamination between samples during processing. A second tweet from the preprint’s lead author, dated 18 July 2019, includes a photo that shows strong potential for cross-contamination between samples in the laboratory.
Finally, it is common practice in insect pathology to use more than one indicator of infection, to reduce the risk of either false positives or false negatives (Lacey 2012; Vega and Kaya 2012). When assessing OrNV infection in CRB, this should include some combination of visual assessment of the gut at dissection, PCR analysis of gut tissue, preparation of histology samples to assess internal changes to the gut lining, and bioassays to determine viral virulence under controlled conditions. All of the OrNV infection rates presented by Etebari et al. are based on a single indicator, i.e. PCR analysis, with a high risk of cross-contamination, such that we consider the OrNV infection rates were overestimated significantly.
In conclusion, we cannot support the assertion of Etebari et al. that OrNV is widespread among new, invasive populations of CRB in the Pacific. Apart from Vanuatu, which was invaded recently by CRB-S without OrNV, the new wave of Pacific invasion is dominated by CRB-G populations without OrNV (Marshall et al. 2017; Reil et al. 2018).
References<br /> AgResearch (2020) Annex 1.1-Distribution map of CRB biotypes and virus. MFAT Progress Report WPG-0101699-DOC-4049125 (June 1, 2020).<br /> Huger AM. (2005) The Oryctes virus: Its detection, identification, and implementation in biological control of the coconut palm rhinoceros beetle, Oryctes rhinoceros (Coleoptera: Scarabaeidae). Journal of Invertebrate Pathology 89, 78-84. <br /> Lacey LA (2012) Manual of Techniques in Invertebrate Pathology (Second Edition), San Diego: Academic Press.<br /> Marshall SDG (2016) FAO Mission Report for Plant Production and Plant Protection TCP/S01/3501 – OTCP140014219: Use and production of Oryctes nudivirus to assist with control of the coconut rhinoceros beetle, Oryctes rhinoceros, in Solomon Islands (August 15, 2016).<br /> Marshall SDG, Moore A, Vaqalo M, Noble A & Jackson TA (2017) A new haplotype of the coconut rhinoceros beetle, Oryctes rhinoceros, has escaped biological control by Oryctes rhinoceros nudivirus and is invading Pacific Islands. Journal of Invertebrate Pathology 149, 127-134. <br /> Ramle M, Wahid MB, Norman K, Glare TR & Jackson TA (2005) The incidence and use of Oryctes virus for control of rhinoceros beetle in oil palm plantations in Malaysia. Journal of Invertebrate Pathology 89, 85-90. <br /> Reil JB, Doorenweerd C, San Jose M, Sim SB, Geib SM & Rubinoff D (2018) Transpacific coalescent pathways of coconut rhinoceros beetle biotypes: Resistance to biological control catalyses resurgence of an old pest. Molecular Ecology 27(22), 4459-4474. <br /> Vega FE & Kaya HK (2012) Insect Pathology (Elsevier Science).
On 2020-08-12 18:27:18, user rob wrote:
This looks really clever. Haven't read it thoroughly, but FYI it looks like there's a typo in the title for Figure 1B - it says regulated, but I believe it should be UNregulated.
On 2020-08-12 15:21:47, user Nicolas Corradi wrote:
This preprint was modified since it last posted on biorxiv.
Readers should now view and cite the published link for the final version, which is linked at the top of this page.
The link to the published version: https://www.frontiersin.org...
On 2020-08-12 14:09:47, user JRLatham wrote:
This will potentially have a significant impact on SARS-CoV-2 origin theories, including our own: https://www.independentscie...
On 2020-08-12 08:37:07, user Andrea Zaliani wrote:
Sirs,<br /> according to your paper's methods, you have performed qPCR experiments as well, but I could not find any table data for it. Could you elaborate?<br /> Best<br /> Andrea
On 2020-08-12 08:02:23, user Asac wrote:
SARS-CoV-2 invades host cells via a novel route: CD147-spike protein<br /> https://www.biorxiv.org/con...
On 2020-08-12 03:45:07, user VGR Subramanian wrote:
As we have studied in Physics, High atomic number materials such as lead are used for effectively absorbing gamma radiations. I am unable to understand being a low Z material, how fungus is able to absorb gamma radiation. Are we talking about very low energy gamma radiations!!!
On 2020-08-11 20:25:20, user Clifton Ricana wrote:
Accepted manuscript found on PLoS Pathogens: https://journals.plos.org/p...
On 2020-08-11 19:10:24, user Romina Garavito-Salini Casas wrote:
"The mutation of C14408T at NSP12 in Indian isolates of SARS-CoV-2 lead to the substitution of proline with threonine." It's wrong, the C14408T mutation substitutes a proline for a leucine.
On 2020-08-11 19:07:53, user Xavier Jenkins wrote:
Generally (always?), phylomorphospace analyses combine a phylogenetic dataset with an unrelated morphometric dataset. Which morphometric dataset was used here? It seems like the Pritchard and Nesbitt 2017 dataset is used both as the tree and the morphological character matrices. Wouldn't this be ill advised?
See Sidlauskas 2008, Clabaut et al 2007, Klingenberg and Ekau 1996, and Santos, Perrard, and Brady for similar applications.
If the assumption here is that phylogenetic characters = functional signal, and that is why the Pritchard and Nesbit dataset was used twice, could it be elaborated upon as to why this decision was made? I question the ecological utility of the characters used in the phylogeny chosen, which was created to address the relationships of Permo-triassic diapsida and early Sauria, and not their functional anatomy.
The discussion (page 11, as well as 34-36) does a good job at explaining why some of the character states could be functional, but I think this could be expanded upon, especially within the main text!
On 2020-08-11 18:12:38, user Xavier Jenkins wrote:
Would it be possible to create a Phylomorphospace plot using the Gauthier et al matrix? Certainly, the taxa included in the Pritchard and Nesbitt taxa are distant enough that any ecological signal would be low at best, if detectable at all. This would probably better elucidate how Oculudentavis fits within squamates more broadly, rather than just the several Toxicoferid taxa (Uromastyx, Shinisaurus, and Iguana) within the Pritchard dataset.
If not, the inclusion of more plesiomorphic species with Pygopodomorpha (or Gekkota more broadly) and Scinomorpha (if even just two taxa) could benefit the analysis, if not just visually.
On 2020-08-11 18:25:46, user Maresca Lab wrote:
Cool manuscript! We are very interested in the ways that MT<br /> polymerization forces can be harnessed for chromosome movements via<br /> chromosome-associated tip-tracking complexes. So, the link between EB1 and Nod<br /> in acentric segregation is quite interesting and thank you for citing our paper<br /> in support of this idea (Ye et al. JCB 2018). I should note that in our 2018<br /> JCB paper we argued that NOD should not be classified as "non-motile"<br /> because dimerized NOD exhibited clear plus-end directed motility. Thus, the<br /> synthetic lethal interaction between I-Cre induction and Nod may be a<br /> consequence of attenuating chromokinesin-mediated sliding (although presumably<br /> KLP3A can still contribute) and the loss of NOD/EB1-mediated polymerization<br /> forces.
On 2020-08-11 16:25:20, user Alex wrote:
So if I correctly understand in your opinion the in vitro RiboLace approach is still useful to detect actively translating transcripts since <br /> puromycin-biotin complex is presumably immobile enough not to detach from the attached actively translating ribosomes? The authors still use cycloheximide to stop the dissociation. Would it imply that there is no need to use any elongation inhibitor in this case?
On 2020-08-11 15:23:26, user Cees van Leeuwen wrote:
Dear Authors,
Your contribution is quite impressive. I have just a minor note. Whereas your generative models cannot achieve the hub connectivity you attribute to gene expression, we have actually shown that generative models can do so. Please check:
Rentzeperis, I. & van Leeuwen, C. (2020). Adaptive rewiring evolves brain-like structure in weighted networks. Scientific Reports, 10, Art. No. 6075.
in which adaptation rewiringis based on diffusion, and perhaps also:
Hellrigel, S., Jarman, N., & van Leeuwen (2019). Adaptive rewiring of weighted networks. Cognitive Systems Research, 55, 205-218.
in which adaptive rewiring is based on synchronization of oscillatory activity. The adaptive rewiring principle works also with more realistic spiking model neurons.
Kindest regards,<br /> CeesvL
On 2020-08-11 01:46:32, user Peter W. Mullen wrote:
I wonder if instant coffee brews also have similar concentrations of H2O2?
On 2020-08-10 14:13:28, user Mina wrote:
I studied that there are a correlation between anti spike antibody and anti nucleoprotein Tcell ,what is reason??
On 2020-08-10 13:35:27, user Cory Bishop wrote:
Great paper! Very interesting to imagine the role of the environment, whether symbiont-produced, or free, in the production of NO for regulation of metamorphosis. One thing I did not see was that the authors considered maternally inherited arginine as an additional source in embryos and larvae. If yes, unfertilized eggs should have some.
On 2020-08-10 11:48:43, user Yi-yi wrote:
No evidence for basigin/CD147 as a direct SARS-CoV-2 spike binding receptor
On 2020-08-07 17:55:14, user Ellie wrote:
By using specialized assays customized to detect specific receptor interactions, researchers from the Wellcome Sanger Institute in Cambridge UK find no evidence for direct binding of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein to a transmembrane glycoprotein known as basigin.
On 2020-08-10 09:32:41, user OxImmuno Literature Initiative wrote:
On 2020-08-10 08:12:03, user OxImmuno Literature Initiative wrote:
On 2020-08-10 08:05:19, user OxImmuno Literature Initiative wrote:
On 2020-08-10 07:56:31, user OxImmuno Literature Initiative wrote:
On 2020-08-09 21:25:46, user Renae Brodie wrote:
Co-author Zahida Sheikh's last name is misspelled on this pre-print, for which I apologize. The correct spelling will appear on the published version of this manuscript.
Renae Brodie
On 2020-08-08 17:41:23, user Babu V. Bassa wrote:
The authors' claim that the the frequency of G614 variant of SARS-CoV-2 in India is only 26% is completely contradictory to the information available through the GenBank and the GISAID databases. The information in these databases also came from India from multiple laboratories. We made our own investigation and found that the frequency of G614 variant in India is at least 90% as of June, 2020. Since this is a very critical matter the authors should make their raw data available publicly (through GenBank etc.). Our results are available at preprints.org (doi:10.20944/preprints202008.0148.v1), as a brief report.
On 2020-08-08 16:14:24, user UAB BPJC wrote:
Review of Benda et al., “The YtrBCDEF ABC transporter is involved in the control of social activities in Bacillus subtilis. <br /> University of Alabama at Birmingham Bacterial Pathogenesis and Physiology Journal Club
Summary<br /> The model organism for genetic competence, Bacillus subtilis, has many uncharacterized methods of regulating its various alternative lifestyles, such as competence, sporulation, and biofilm formation. As far as competence goes, most of these methods interact in some way with the transcription factor ComK, whether directly or indirectly. This paper focuses on the characterization of the ytr operon and its role in the development of competence. <br /> Overall, the paper takes a sound and methodical approach to the genetic testing of the operon, and the role of the ytr operon it proposes is convincing. However, we do have some comments that may be beneficial to the paper if they are addressed.
General Comments<br /> • There seems to be a general lack of statistical analysis throughout the tables in the paper. This may be just a lack of explanation of the stats that were performed, but we found ourselves asking what the “+/-“ was referring to in the data points. Is this the standard deviation? A slightly more in-depth explanation of this would be helpful.<br /> • Towards the end of the paper, namely in the last two figures, we felt that the data seemed a little scarce in comparison to earlier tables. Since a wide variety of ytr mutants were created, would it be possible to analyze biofilm formation and cell wall thickness with them?
Specific Comments<br /> • In Table 4, we feel it would be very helpful to include a representative image of the fluorescence microscopy.<br /> • As mentioned in above, the cell wall thickness assay only includes two mutants in comparison to the wild-type, but it would be beneficial to include a wide range of the ytr mutants (especially the ytrAF knockout) and others that exhibited a low number of transformants to potentially determine a correlation of cell wall to transformation efficiency.<br /> • Also on Figure 3, it may be worth staining and imaging pili on the ytrA mutant, since it is speculated that the thicker cell wall phenotype could be inhibiting them.<br /> • In the text leading up to Table 4, it is mentioned that the RNases were not included because of their tendency to form chains. However, the nrnA mutant is till imaged. Is there a reason to believe it won’t form a chain unlike the mutants that aren’t included?
On 2020-08-08 00:30:12, user Ludmila Prokunina-Olsson wrote:
I would like to point out that 3 recent preprints (including ours) showed that ACE2 is NOT induced by IFNs and viral infection but a truncated ACE2 isoform (dACE2) is. Unfortunately, microarrays would not capture this important difference. Let's not repeat the statement that expression of ACE2 increased by IFNs and viruses will increase SARS-CoV-2 infection.
On 2020-08-07 17:18:38, user E. Laurel wrote:
This is really interesting work. Have you subtyped the cell lines and PDX models you're using? I'd be interested in seeing if classical and basal lines responded differently or had different base levels of DDR1 or NETs. Perhaps this is one targetable difference between the subtypes or maybe it would work on all patients.
On 2020-08-07 05:52:10, user Brad wrote:
A counterscreen is needed, and would most likely show most the hits are classic false-positives.
On 2020-08-07 01:38:52, user Trieu-Duc Vu wrote:
In this study we described for the first time the emergence of a "energy-saving strategy" among individuals of fighting fish B. splendens males after their conflicts have been resolved.
On 2020-08-06 21:16:21, user Amr Sawalha, MD wrote:
This is now published in a peer-reviewed journal<br /> https://www.nature.com/arti...
On 2020-08-06 18:37:40, user Luis Diambra wrote:
the new version of this preprint was accepted in Frontiers<br /> https://www.frontiersin.org...
On 2020-08-06 15:57:22, user Gioele La Manno wrote:
Susaki EA/suishess Thank you for bringing this study to our attention! We were not aware of its existence. Despite our technique being very different from the one described in this paper, at both the mathematical and the technical level, I agree that this pioneering work from Okamura-Oho and collegues, should be cited in our paper.<br /> We will include the citation on a revised version.<br /> Thank you again for the heads-up.
On 2020-08-06 00:22:41, user Susaki EA/suishess wrote:
Interesting. The idea seems to have been originally tested with microarray in Okamura-Oho et al. PLOS ONE 2012 7(9): e45373. Should the study be referenced?
On 2020-08-06 10:03:12, user Ian Keesey wrote:
Full text now available via eLife (https://elifesciences.org/a.... Insights and commentary on this research are also now available (https://elifesciences.org/a....
On 2020-08-06 09:00:32, user NimwegenLab wrote:
Please see our response to this comment at: https://www.biorxiv.org/con...
On 2020-08-06 06:33:34, user Yu-Chen Ling wrote:
This article is published in the journal Soil Biology and Biochemistry entitled "Bacterial predation limits microbial sulfate-reduction in a coastal acid sulfate soil (CASS) ecosystem" (https://doi.org/10.1016/j.s.... You are welcome to read or download it through this link before September 22, 2020: https://authors.elsevier.co...
Another two publications in the same project are:<br /> Ling, Y.-C., Berwick, L., Tulipani, S., Grice, K., Bush, R., Moreau, J.W., 2015. Distribution of iron- and sulfate-reducing bacteria across a coastal acid sulfate soil (CASS) environment: implications for passive bioremediation by tidal inundation. Frontiers in Microbiology 6, 624. https://doi.org/10.3389/fmi....<br /> Ling, Y.-C., Gan, H.M., Bush, M., Bush, R., Moreau, J.W., 2018. Time-resolved microbial guild responses to tidal cycling in a coastal acid-sulfate system. Environmental Chemistry 15, 2–17. https://doi.org/10.1071/EN1...
On 2020-08-05 19:08:23, user Terri Ellen wrote:
There is no discussion of hormone levels during the period, any testing done at all that evaluated what T and E levels were during this time and how good T suppression was in the trans women? Very poor methodology here.
On 2020-08-05 18:11:13, user Paul Gordon wrote:
Thanks for posting this, will your S# consensus sequences be made available in GISAID or the NCBI? I did not see any accession numbers in the manuscript.
On 2020-08-05 15:22:24, user izzonj wrote:
Thank-you for posting this manuscript it is very interesting. i would like to comment about your statement: . "Activation of Sigma-2 receptor signaling has been shown to induce apoptosis and cytotoxicity [9]"
I would like to call your attention to the following publication and consider its implications for interpreting data in the field of sigma-2 ligands and their cytotoxic effects.
Zeng C, Weng C-C, Schneider ME, Puentes L, Riad A, Xu K, Makvandi M, Jin L, Hawkins WG, Mach RH: TMEM97 and PGRMC1 do not mediate sigma-2 ligand-induced cell death. Cell Death Discov 2019; 5:58
Best regards,<br /> N Izzo
On 2020-08-05 10:33:59, user Small Cat wrote:
Interesting article! I do wonder about the "completeness" of the 3 PW databases mentioned; if I'm correct, PW databases do not cover more then 60% of the total amount of proteins. You compare the gene sets between database; it would also be interesting to know which area's are missing within these 2 databases, to put your results in (more) perspective.
On 2020-08-05 04:27:42, user Marco wrote:
is excellent publication. ¿what relation with window 8 hrs and edema?
On 2020-08-05 02:26:28, user Eli Boritz wrote:
Very interesting work! Fascinating if mutations accumulating in SARS-CoV-2 worldwide are due to host cell enzyme with targets that are predictable. Implications for immune escape and targets of drug therapies.
Is it at all possible that some of the similarity in mutation signatures between datasets results not from virus mutations in vivo, but from technical sources? For example, consistent mutational signatures of PCR enzymes used to amplify both types of viruses?
On 2020-08-04 19:56:05, user Aditya Iyer wrote:
Excited to be a part of this work. Looking forward to hear suggestions/criticisms and of course questions! Feel free to contact us for more information!
On 2020-08-04 15:09:42, user Fraser Lab wrote:
https://www.biorxiv.org/con...
Discovery of a cryptic allosteric site in Ebola’s ‘undruggable’ VP35 protein using simulations and experiments
In this manuscript, Cruz and co-workers search for cryptic pockets in the interferon inhibitory domain (IID) of Ebola’s viral protein 35 (VP35). VP35 is of interest because it is suggested (although without citations to failed HTS efforts, etc) that it might be undruggable and it might be a good therapeutic target. They use a suite of simulations and analysis tools to identify a “cryptic” site, which partially overlaps with FT map assessment and may overlap with the binding site for the backbone of dsRNA. A major issue with the manuscript is that we are never oriented to these surfaces properly (Figure 1 is not oriented like others, it is not clear which chain is which, and the colors are confusingly overlapping with the orange/blue in other figures) - and we have no idea what the 3D shape of the new cryptic site looks like at its most open. Figure 3D starts to get at how it distorts a model of binding at the other RNA site, but it’s a bit unclear too, especially given the potential for overlaying the existing structure in Figure 1 to show the loss of contacts. This and the jargony term “exposon” were both sources of great frustration in reading what appears to be an excellently executed simulation section.
The interpretation of the thiol-labeling results does not seem to rest on completely solid ground. In particular how specific labeling rates were segregated and assigned to specific cysteine residues, is not clear. Table S3 (why are unfolded rates so different) and Table S1 (why are rates in C275S so perturbed - 10X!) give the raw data for assignment, but it doesn’t quite square up. Understanding this assay is truly essential for the reader to believe that the authors are observing the cryptic pocket opening (e.g. rates of C307 and C326 reacting with DTNB will be faster when the pocket is open, because only then are these residues solvent exposed). Are there mutations predicted to shift the “exposon” (ugh that term) - towards the ground state that would reduce the labelling or slow the rate?
Next, they use an FP assay, which could also potentially be useful in more traditional HTS or fragment based methods to identify chemical matter, to validate the labeling with a functional read out. There are several potential explanations for the observed shift, as their data are limited by solubility. Are there other methods to detect this that rely on the protein at low concentration, but have the substrate titrated? The experiment would really benefit from a control (quadruple Cys > Ser mutant, where DTNB wouldn't react). Why is the modified protein less soluble (and doesn’t that set off some red flags)? Why does the effect seemingly go away with the overhang there (blue square data points)? Should there be some cooperativity in the labelling if the exposons (ugh) are coupled?
In summary, excellent simulations show a pocket (likely - hard to say from the images we see) that may have some interesting properties - but that case is not really nailed, yet..
Minor issues<br /> The CD experiment lacks method details. Figure 5B lacks details on the CD setup that would typically be found in a figure legend, such as solvent, pH, temperature, and concentration of protein used.<br /> In the results, “After running FAST, we gathered additional statistics…”. What additional statistics?<br /> In the results, “Unfortunately, disrupting backbone binding is of less therapeutic utility than disrupting blunt end binding and it is unknown whether the contacts between A306, K309, and S310 are essential for backbone binding.” Is there a reference for this?<br /> In the results, the fourth paragraph under “The cryptic pocket is allosterically coupled to the blunt end-binding interface” needs attention. Twice, it is mentioned “we performed a dimensionality reduction”. The first time is in the first sentence, and the second time is after other analyses and what came out of them are discussed. Do the authors neglect the results of their first dimensionality reduction? Or do they mention doing it too early in this paragraph and actually perform it after comparing magnitudes of the CARDS analyses (the heat map in Supp. Fig. 2), in which case this paragraph should not open with saying “we performed a dimensionality reduction”, because the order of events in this paragraph is confusing. It seems to me that the latter is the case.<br /> In the results, “To test whether the observed labeling could be due to an alternative process, such as global unfolding, we determined the population of the unfolded state and unfolding rate of VP35’s IID under native conditions (Supplementary Table 2) and the intrinsic labeling rate for each cysteine (Supplementary Table 3).” How were these populations determined? Was a model used? There are no details in the results or methods sections. Under Supplementary Table 2, it’s said these data are from denaturation data and intrinsic tryptophan fluorescence. Shouldn’t details of these experiments be in a methods section somewhere? A supplementary methods section, perhaps?<br /> In the methods section under “Molecular dynamics simulations and analysis”, it is said simulations were initiated from chain B. Is there a reason to have chosen chain B? Would choosing another IID chain have led to some differences in the results?<br /> “"making it a reasonable surrogate for the type of effect one might achieve with a fragment hit." - but covalency needs to be acknowledged here! it’s not apples to apples in this way.
Stylistic issues / minor points<br /> Inconsistency with capitalization of the full name of DTNB. In the results, it is as such: 5,5’-Dithiobis-(2-Nitrobenzoic Acid). In the methods, it is completely in lower case.<br /> Inconsistency with labeling nomenclature in Figure 5; e.g. “IID” in 5A versus “VP35 IID” in 5B.<br /> Add comma<br /> “Our final model has 11,891 conformational states, providing a detailed characterization of the different structures the IID adopts[,] but making manual interpretation of the model difficult.”<br /> “The dihedral level couplings were coarse-grained into residue-level coupling by summing the total coupling between all the relevant dihedrals and the network was filtered to only retain significant edges.59”<br /> OPT 1: by summing the total coupling between all the relevant dihedrals, and the network was filtered<br /> OPT 2: relevant dihedrals and [by] filtering the network to only retain...<br /> It's one or the other, and they have different meanings. It is unclear which meaning is meant as written.<br /> “Various concentrations of DTNB were added to protein[,] and change in absorbance was measured in either an SX-20 Stopped Flow instrument (Applied Photophysics, Leatherhead, UK), or an Agilent Cary60 UV-vis spectrophotometer at 412 nm until the reaction reached steady state (~300 s).”<br /> Typos<br /> “Since the cryptic pocket does not coincide with the blunt end-binding interface, our results suggests the impact on dsRNA binding is allosteric.”<br /> Supplementary Table 4 uses “56FAM-” and “56-FAM-”.<br /> Confusing wording<br /> “Such pockets are absent in available experimental structures because they only form in a subset of excited states that arise due to protein dynamics.” <br /> What do you mean by “available experimental structures”? "Available" is vague. I'd flip this sentence structure around to say: "Cryptic pockets only form in a subset of excited states that arise due to protein dynamics" and are therefore not captured in the blurred/averaged/word Xray protein structure.<br /> Also, this “available” wording is also in the abstract and in the first sentence under the thiol labeling section of the results, except that there it is “available crystal structures”. I’m less confused about its meaning now that I see it referring to crystal structures specifically. It makes more sense here than in the first case I brought up.<br /> “Since the cryptic pocket does not coincide with the blunt end-binding interface, our results suggests the impact on dsRNA binding is allosteric.”<br /> The use of “coincide” here is confusing. It would be clearer to say that, when the cryptic pocket is open, blunt end-binding is unable to take place. Perhaps: “Since blunt end-binding is unable to take place when the cryptic pocket is open, our results suggest the impact of the open cryptic pocket has on dsRNA binding is allosteric.”<br /> “Repeating our FP assay with TNB-labeled protein reveals that labeling allosterically reduces the affinity for blunt-ended dsRNA by at least 5-fold (Fig. 5A).”<br /> It would be beneficial to clarify that the TNB-labeled protein is the C247S/C275S variant. It is mentioned in the referenced figure legend, but it would be helpful to also have it here.<br /> Supplementary Figure 6 is mislabeled as a second Supplementary Figure 5.
James Fraser and Jenna Pellegrino (UCSF), we were prompted to review this by a journal in March, got delayed in finalizing it due to COVID-19 and are posting it now.
On 2020-08-04 14:29:18, user John L wrote:
This article has been presented in a 15-minute talk at https://jrnlclub.org/resear...
On 2020-08-04 14:03:35, user Prakash Ananth wrote:
Please could you share the additional files.
On 2020-08-04 12:28:45, user Raccoon wrote:
Q1-Why don't they just isolate and purify the virus according to the scientific method (Koch’s postulates) and that would settle it, instead of putting particles together to represent a virus?
No one so far has answered the question above. Q2- And how if they have not isolated and purified the virus according to the specific proteins how would they accurately make a vaccine that works?
On 2020-08-04 08:20:35, user OxImmuno Literature Initiative wrote:
On 2020-08-04 08:13:06, user OxImmuno Literature Initiative wrote:
On 2020-08-04 08:10:14, user OxImmuno Literature Initiative wrote:
On 2020-08-04 08:06:21, user OxImmuno Literature Initiative wrote:
On 2020-08-04 08:03:34, user OxImmuno Literature Initiative wrote:
On 2020-08-04 07:54:45, user OxImmuno Literature Initiative wrote: